Aerogel compositions

ABSTRACT

The present invention relates to gel compositions comprising at least one entrapped active component.

FIELD OF THE INVENTION

The present invention relates to the field of gels and the use of gelsas means for storage and controlled release of component therefrom.

BACKGROUND OF THE INVENTION

Sol-gel chemistry has been used for many years. Most research has beendirected towards inorganic gels created by hydrolysis of metalalkoxides. NASA has developed aerogels where the strength and the heatinsulation properties of these materials have been optimized. Many otherscientists have been reporting on the use of gels and aerogels forcontrol of drug delivery. Here the gel performs the role as a spongeabsorbing medically active compounds for later slow release. The processof interest is here diffusion out of the inert gel material. Yet anotherdirection of research has been to encapsulate large molecules likeproteins or even live bacteria or cells into the gel network. It hasbeen found that in many cases the enzymes encapsulated in the gel retaintheir activity. In special cases as observed with Lipases they may evendisplay significantly enhanced activity when located in the gel network.The gel is thus used as a bioreactor where the enzyme is staying fixedwhile the reactants and the products diffuse in and out of the very opengel network. Also in these last two situations it is important that thegel is strong and that it can retain its properties during theprocesses.

Aerogel particles have been proposed for use in controlled release ofpharmaceuticals, see e.g. U.S. Pat. No. 6,994,842 B2.

Active compounds are a necessity for protection against biologicalgrowth in the coatings field. Due to environmental restrictions againsttraditional biocides and fungicides the need for more environmentallyacceptable solutions is growing. Even though attempts to use enzymesand/or other organic molecules can be found in literature the success isrestricted.

Incorporating this type of molecules in a paint or coating is not aneasy task.

In paints containing enzymes such as proteases the water-borne systemsmay have stability problems since sedimentation during storage result ina pigment and binder precipitate and a water enzyme liquid phase. Duringstorage the enzyme react in an autodegradation whereby the enzymeactivity is significantly reduced. For this purpose it would be highlysignificant if the enzyme could be prevented from degradation duringstorage.

There is also a need to keep the active compound on the coating surfacein an effective dosage to get a proper protection.

Furthermore it must be considered that different types of coatingsdepending on the application probably will need different solutions tothe dosage problem.

Aerogels have been known to be useful as additives in paint formulationssince they among other properties may introduce thixotropic properties.This property allows industrial spraying of thicker films of goodquality. WO 2002/074868 discloses thixotropic paint formulationscomprising silica aerogel.

SUMMARY OF THE INVENTION

In order to overcome the above-mentioned limitations of the knowncompositions for entrapment, storage and subsequent controlled releaseof an active component, the present invention provides a compositioncomprising a gel wherein is entrapped at least one active component suchthat release of said at least one active component from said compositionis substantially caused by degradation of said gel.

In one aspect the present invention relates to a composition comprisingan aerogel wherein is entrapped at least one active component such thatrelease of said at least one active component from said composition issubstantially caused by degradation of said aerogel.

In one aspect the present invention relates to a composition comprisingan wet gel wherein is entrapped at least one active component such thatrelease of said at least one active component from said composition issubstantially caused by degradation of said gel. The gel is prepared ina solvent mixture identical in composition to the paint in which it isplanned to be incorporated.

In one embodiment of the invention said at least one active componentsubstantially is not liberated from said composition by diffusion out ofsaid composition.

DEFINITIONS

The term sol as used herein means a solution of various reactants thatare undergoing hydrolysis and condensation reactions. The molecularweight of the oxide species produced continuously increases. As thesespecies grow, they may begin to link together in a three-dimensionalnetwork.

The term alcogel as used herein means a wet gel which can be removedfrom its original container and can stand on its own. An alcogelconsists of two parts, a solid part and a liquid part. The solid part isformed by the three-dimensional network of linked oxide particles. Theliquid part (the original solvent of the Sol) fills the free spacesurrounding the solid part. The liquid and solid parts of an alcogeloccupy the same apparent volume.

The term supercritical fluid as used herein means a substance that isabove its critical pressure and critical temperature. A supercriticalfluid possesses some properties in common with liquids (density, thermalconductivity) and some in common with gases (fills its container, doesnot have surface tension).

The term aerogel as used herein means what remains when the liquid partof an alcogel is removed without damaging the solid part. Removal of theliquid part can be achieved by e.g. supercritical extraction. If madecorrectly, the aerogel retains the original shape of the alcogel and atleast 50% (typically >85%) of the alcogel's volume.

The term xerogel as used herein means what remains when the liquid partof an alcogel is removed by evaporation, or similar methods. Xerogelsmay retain their original shape, but often crack. The shrinkage duringdrying is often extreme (˜90%) for some xerogels.

The term cryogel as used herein means what remains when an alcogel isfrozen and the previously liquid part of the alcogel is removed byevaporation keeping the alcogel frozen all the time. Cryogels may retaintheir original shape, but often crack. The shrinkage during drying maybe substantial for some cryogels. Addition of suitable surfactants inthe alcogel may relieve this problem.

The term substantially as used herein means considerably such as whenexpressed as a percentage at least 25%, such as at least 40%, such as atleast 50%, such as at least 75%, such as at least 85%, such as at least95%. For instance “release of X is substantially caused by degradationof said gel” means that release of X is caused considerably bydegradation of said gel.

DETAILED DESCRIPTION OF THE INVENTION

The present invention reverse in a sense the priorities and therebyproviding a new area of applications.

In the invention molecules are entrapped in the gel, e.g. during theSOL-GEL process. Since pores in the gel frequently will be between 1 and20 nm the network is capable of encapsulating large molecules where thegel network creates bottleneck for passing. Other smaller molecules maybe retained by the strong interaction with the cavity walls in the gel.Thus the molecules claimed to be of interest for the invention aremolecules displaying no pronounced tendency to leach out of the gel.

This encapsulation of organic molecules set the loaded gels apart fromthe first class of applications mentioned above. The focus on moleculespermanently entrapped in the gel set the invention apart from the secondclass. The entrapment still concurs with the third class.

The loaded gel prepared in the liquid form or as an aerogel, cryogel orxerogel is designed by its chemical composition to be degradable underthe conditions where it is planned to be used. The degradation may bechemical—as it happens with hydrolysis in water—where the pH of thewater strongly influences the hydrolysis rate of metal alkoxy basedgels. The degradation may however be purely mechanical as it isoccurring when grains of the gel are present at a surface where frictionwear down the grains.

By this design the gel differs markedly from the classes 2 and 3 and inmost cases from class 1 since optimization of strength occur for acompletely different set of criteria in the space research.

The encapsulation of molecules in the gel may have a number of effectsto be exploited in the present invention changing the release profileduring gel decomposition.

-   -   They may be protected against degradation as an effect of their        spatial confinement    -   They may be showing increased thermal stability due to their        interaction with the gel structure    -   They may show improved stability towards irradiation stability        due to their interaction with the gel structure    -   Their release will be controlled by the degradation of the gel        lattice    -   Molecules may be functionalized in such a manner that the        functionalized molecule can be acting as an active component in        the network formation. The covalent binding to the gel network        may result in a release of the active compound still linked to        fragments of the gel network.

Often it is a problem to disperse a hydrophilic substance in ahydrophobic solvent and visa verse. By inclusion of the substance in thegel it is possible to control the distribution in the solvent bytailoring the polarity of the gel.

-   -   Hydrophilic biomolecules may be included in a hydrophobic gel        thereby ensuring their homogeneous distribution in a hydrophobic        solvent.    -   By production of an aerogel, cryogel or xerogel the release will        be determined by the grain size and composition of the Gel.    -   Many variations of the gel structure are possible in order to        control degradation. They include mixing of various metal        alkoxides, introduction of alkyl or aryl substituents on some of        the alkoxides    -   The gel properties may also be modified by introduction of        polymers as part of the original sol. Subsequently they will be        entrapped and end up as part of the gel network.    -   A manufacturer may optimize a composition including gel        including one entrapped species. Replacement of the entrapped        species with another does not require renewed optimization since        the gel retains its physical properties independent of the        entrapped species.    -   Several gels with different entrapped species may be mixed as        powders to obtain a desirable effect.    -   Several active compounds may be incorporated in the same sol/gel        since the species are entrapped individually their effects are        not affected by potential mutual interactions    -   The sol gel process may be carried out in such a manner that two        or more different compounds are entrapped in different regions        of the same gel. This requires the gelation process to be        interrupted for each addition of an entrapped species.    -   Two or more compounds may be entrapped and selected so that upon        their release they can chemically react whereby new products are        formed. An enzyme and a substrate may serve as an example. The        reaction products may be small highly reactive molecules

The gels prepared according to this invention are foreseen to haveapplication in

-   -   Coatings in general, e.g. paint, ink, lacquer products where the        film thickness warrants the integration of gel structures.    -   In surfaces on medical devices    -   In plast composites    -   The known property as a thixotropic component in coatings may be        combined with the properties obtained by this invention    -   As a consequence of the regulations on chemicals and biocides        derivatives of active molecules are considered as new species        requiring individual risk assessments. By entrapment the        molecules are not chemically modified but their effects are        controlled. This may result in considerable time and financial        savings.

Silica aerogels may be prepared according to traditional microparticlesol-gel processing.

Solvent Based Coatings.

Even though the use of solvent-based coatings has been restricted it isstill an area of importance. Introducing an aerogel in a solvent-basedpaint has the following effects:

-   -   Structure is introduced into the wet paint at low shear rates    -   The degradation rate of the coating increases    -   Water up-take is increased compared to coatings without        aerogels, but still low due to the fact that solvent-based        coatings are normally very dense    -   The release of an active substance can be controlled as the        release will be related to the degradation effect

As possible application areas traditional solvent-based paints foroutdoor protection can be mentioned. It should be acknowledged that thechoice of the optimal binder systems used is important. The aboveconcept based on degradation over time can mainly be used on materials,where the degradation time is acceptable. One example is coatings forwood (alkyds have always degraded due to the climate (sun and rain)),roofs, etc.

It should be mentioned that during the grinding process of thepaint/coating there will be a small not intentional release of theactive compound from the aerogel due to mechanical forces applied to thesurface of the formulation. The proportion of active compound release isnot expected to be significant as the aerogel particles aimed for in thepaint still have a small surface to volume ratio.

Water-Borne Coatings.

There is a demand for water-borne coatings in general. Water-bornecoatings are used on a large scale for architectural paints, woodprotection etc. But at the same time water-borne coatings are used on avery small scale in the yacht market and heavy-duty products. As anexample an anti-fouling yacht paint can be mentioned.

To achieve a desired polishing rate the coating has to degrade due tomechanical friction.

The parameters that influence the polishing rate is the choice ofbinders, their concentration as well as the choice of pigments/fillersand their concentration.

Introducing a gel in a water-borne anti-fouling paint has the followingeffects:

-   -   The polishing rate of the coating increases    -   Water up-take is increased significantly compared to coatings        without aerogels

The water up-take can be reduced in several ways:

-   -   Introducing a hydrophobic agent, which probably is not enough on        its own    -   Changing the gel composition and thus making the film more water        resistant.

It is relevant to reduce water up-take to achieve a commerciallyacceptable anti-fouling paint.

It should be mentioned that water-borne coatings are very importanttoday. Outdoors it is crucial to achieve protection against bio-films onwood, houses, roofs etc.

But also indoors problems with bacteria and fungi are essentialespecially in wet rooms.

In another aspect the present invention provides an gel modified by aninterpenetrating network of a polymer. The polymer is chosen to fulfilthe criteria:

-   -   1. it is water soluble or dispersible    -   2. it is compatible with the formation of the gel network    -   3. it is actively promoting the molecular dispersion of for        example a biomolecule, e.g. an enzyme, in the gel network. If        this is not possible the polymer should be acting as a neutral        component not hampering the dispersion of the biomolecule, e.g.        an enzyme, in the gel network.    -   4. The interpenetrating polymer aerogels network should result        in particles that may be dispersed in the organic phase of the        liquid paint    -   5. The polymer should reduce the water uptake or water uptake        rate in the aerogel in such a manner that the polishing rate for        the paint film is reduced.    -   6. The molecular weight of the polymer should be so large that        physical entanglement in the aerogel leads to an efficient        immobilization. At the same time the polymer molecular weight        should not exceed the limit where its introduction in the        gel-forming step would result in an unacceptable increase of the        viscosity.

As a nonexclusive criterion it is relevant to include polymers where theenvironmental and toxicological clearances already have been obtained.Examples of such substances are polyethyleneglycols, polylactic acid,polyvinylalkohol, polyvinylpyrrolidone, poly-lysine, heparins,poly-hyaluronic acid, polysaccarides and many more.

The gel is typically silica based. The silicon may fully or partly bereplaced by other tri- or tetra-valent metal ions.

According to another aspect of the present invention it is possible tostore, preserve and release enzymes from an gel used as a component in asurface film. In the case of biofouling a bacterial film is rapidlyformed on the surface. The success of the aerogel containing enzyme relyon the controlled availability of sufficient large quantities of enzymeat a give time to impede or reduce the evolution of the biofilm and thesettlement of algae, mussels and barnacles in the bacteria film.

Various enzymes may be suitable as active components in the compositionof the present invention.

In one embodiment the at least one enzyme or protein comprises at leastone enzyme selected from the group consisting of hemicellulolyticallyactive enzymes, amylolytically active enzymes and/or cellulolyticallyactive enzymes.

In another embodiment the one or more bioactive agent(s) comprisesendopeptidases.

In one embodiment the endopeptidase(s) comprises a Subtilisin (EC3.4.21.62). The Subtilisin (EC 3.4.21.62) has the followingcharacteristics: (i) optimum activity at a pH in the range of about7-10, and (ii) optimum activity at a temperature in the range of about55-65° C. The Subtilisin (EC 3.4.21.62) is in one embodiment Alcalase.

In one embodiment the hemicellulolytically active enzyme(s) is selectedfrom the group consisting of Endo-1,4-beta-xylanase (E.C. 3.2.1.8),Xylan endo-1,3-beta-xylosidase (E.C. 3.2.1.32). Glucuronoarabinoxylanendo-1,4-beta-xylanase (E.C. 3.2.1.136), Betamannosidase (E.C.3.2.1.25), Mannan endo-1,4-beta-mannosidase (5 E.C. 3.2.1.78) and Mannanendo-1,6-beta-mannosidase (E.C. 3.2.1.101). In another embodiment thehemicellulolytically active enzyme is a xylanase. In one embodiment thexylanase is an endo-1,4-beta-xylanase (E.C. 3.2.1.8).

The amylolytically active enzyme(s) can in one embodiment be an amylase.

In another embodiment the one or more amylolytically active enzyme(s) isselected from the group consisting of α- and β-amylases,amyloglucosidases (E.C. 3.2.1.3), pullulanases, α-1,6-endoglucanases,α-1,4-exoglucanases and isoamylases.

The one or more amylolytically active enzyme(s) can also beamyloglucosidase.

In one embodiment the amyloglucosidase is an 1,4-alpha-glucosidase.

In one embodiment the anti-fouling composition agent comprises one ormore gel(s) and at least one xylanase and at least one amyloglucosidase.

In another embodiment the anti-fouling composition agent comprises oneor more gel(s) and at least one endo-1,4-beta-xylanase (E.C. 3.2.1.8)and at least one 1,4-alpha-glucosidase (E.C. 3.2.1.3).

In yet another aspect the present invention provides an aerogelcomprising bacteriophages. Bacteriophages are much smaller than thebacteria they destroy—usually between 20 and 200 nm in size.

They have been used for over 60 years as an alternative to antibioticsin the former Soviet Union and Eastern Europe. Bacteriophages areviruses targeting and preying on bacteria. In this sense they areuniversally present in low concentrations. They are highly specific andtherefore constitute no danger for species outside the family ofbacteria for which they are targeted.

Bacteriophages are not capable of multiplying unless they are prying onthe bacteria they target. They are seen as a possible therapy againstmulti drug resistant strains of many bacteria. As complex proteins theythemselves can naturally be attacked and consumed by other organisms.

From a suspension containing Bacteriophages they may be immobilized byconversion of the suspension to a hydrogel. Several patents and articlesdescribe this procedure. Once encaged in the gel network the

Bacteriophages are restricted in their motion and they cannot getcontact to the bacteria the pray on. Conversely the organisms that mightconsume the Bacteriophages cannot get access to them due to the gelnetwork. The hydrogel network may by a suitable treatment bedisintegrated to small fragments the size of micrometers. Still thebacteriophages will be encapsulated in these fragments. These smallfragments may be distributed in a paint formulation and be applied tocreate a coating. During degradation (with antifouling paint it will bepolishing rate) of the paint bacteriophages will slowly be released. Ifa biofilm with the target family of bacteria grows on the surface of thepaint the bacteriophages will rapidly attack the bacteria and multiplyas long as the family of bacteria is present on the surface. Theconstant release of a low dose of bacteriophages will stabilize thisscenario and prevent the formation of colonies of bacteria of theselected type. In August, 2006 the US Food and Drug Administration (FDA)approved using bacteriophages on cheese to kill the Listeriamonocytogenes bacteria, giving them GRAS status (Generally Recognized AsSafe). In July 2007, the same bacteriophages were approved for use onall food products.

From biological studies of early settlement on clean surfaces it isknown, that the colonization of a given surface typically is performedby a limited number of bacteria. The species performing this functionmay vary in different regions on the globe. It is completely feasible touse a cocktail of several relevant bacteriophages in the formation ofthe hydrogel. Hereby the attack on the biofilm bacteria will be on allthe relevant bacteria and the resulting destruction of the biofilm morecomplete.

Non-limiting examples of lytic bacteriophages suitable for usedaccording to the present invention is λ phage-lysogen, T2 phage, T4phage, T7 phage. T12 phage, R17 phage, M13 phage, MS2 phage, G4 phage,P1 phage, P2 phage, Phi X 174 phage, N4 phage, Φ6 phage, Φ29 phage and186 phage.

For the practical use of the invention within paints based on organicsolvents it will not suffice to create a hydrogel. Following normalprocedures the gel particles should be suspended in the organic phase ofthe paint. Here hydrogels are a poor choice since they will be polar andincompatible with the organic phase. For most applications theconversion of the hydrogel to an aerogel/cryogel will be required. Afterthis conversion the dried gel can be suspended in the organic phase.This ensures a better distribution in the coating film and a betterstorage stability.

It is central to this invention that it is possible to convert thehydrogel into aero/cryogel without significant losses in bacteriophageactivity.

The present invention relates to the following aspects:

-   -   1. Use of a gel containing Bacteriophages as a component of an        antifouling paint or other antibacterial paint/lacquer and        coatings    -   2. preparation of an aerogel containing Bacteriophages as a        component of an antifouling paint and coating    -   3. preparation of a cryogel containing Bacteriophages as a        component of an antifouling paint and coating    -   4. preparation of a xerogel containing Bacteriophages as a        component of an antifouling paint and coating    -   5. preparation of an aerogel/cryogel/xerogel containing        Bacteriophages that may be released in an active form from the        gel.

The invention does not chemically modify the bacteriophages. Thereforethey introduce no new substances to the environment.

The gelforming substances has been chosen to be based on metal oxidesbenign to the organisms and the environment.

EXAMPLES Example 1 Enzymes Incorporated in a Silica Aerogel ForSolvent-Based Paints and Coatings

1) 57.4 g TMOS (Tetramethyl orthosilicate 98% from Aldrich) and 229.2 gMethanol (Methanol reagent PH. EUR. from Bie & Berntsen) was mixed on amagnetic stirrer in a 1 L Erlenmeyer flask for 15 minutes.

2) 200 mL Esperase solution (HPF from Novozymes) was dialysed and freezedried. There was obtained 18.40 g dry enzyme, which was dissolvedquickly (about 5 minutes) in 60 mL milli-Q water and the viscoussolution was added drop wise to 1) during mixing. The solution was mixedfor additionally 15 minutes.

3) 0.933 g of ammonium hydroxide (28-30% solution from Bie & Berntsen)dissolved in 7.50 g of milli-Q water was added dropwise to 2) duringmixing at full speed (1500 RPM) on the magnetic stirrer. Afteradditionally 2 minutes of mixing, the white opaque solution wastransferred into a 1 L bluecap bottle. After approx. ½ hour, thegelation took place and the obtained 410 mL gel was aged in methanol,for 24 hours at room temperature, before drying.

4) 287 g of the wet gel from 3) was cut into smaller pieces andtransferred under methanol to a ½ L pressure vessel (½ L flow reactor,equipped with heating jacket and metal frits in both ends, from Thardesigns). There the gel was flowed with ½ L of methanol at 0.5 mL/min.Then the temperature in the heating jacket was raised to 50° C. and thepressure raised to 100 bars, at a rate of 3 bars/min. During 8 hours at50° C. and 100 bars, 2½ kg of CO₂ was flowed through the vessel at arate of approximately 6 mL/min measured at 10° C. After flowing thepressure was slowly released during several hours. The weight of thesupercritical dried aerogel was 34.23 g.

Example 2 Enzymes Incorporated in a Silica Aerogel For Water-BornePaints and Coatings

1) 28.6 g TMOS (Tetramethyl orthosilicate 98% from Aldrich) and 111.0 gMethanol (Methanol reagent PH. EUR. from Bie & Berntsen) was mixed on amagnetic stirrer in a 1 L Erlenmeyer flask for 15 minutes.

2) 0.752 g PVA (Polyvinyl alcohol, with a degree of polymerisation of2000 and a degree of hydrolysation of 86-89 mol %, from Fluka Chemika)was wetted with 5 mL methanol and dissolved in 30 mL milli-Q water. 100mL Esperase solution (HPF from Novozymes) was dialysed and freeze dried.Thereby 6.279 g dry enzyme was obtained, which was dissolved quickly(about 5 minutes) in the PVA solution and the obtained viscous enzymesolution was added drop wise to 1) during mixing. The solution was mixedfor additionally 15 minutes.

3) 0.517 g of ammonium hydroxide (28-30% solution from Bie & Berntsen)dissolved in 3.737 g of milli-Q water was added dropwise to 2) duringmixing at full speed (1500 RPM) on the magnetic stirrer. Afteradditionally 2 minutes of mixing, the white opaque solution wastransferred into a 1 L bluecap bottle. After 15 minutes the gelationtook place and the obtained 200 mL gel was aged in methanol, for 24hours at room temperature and additionally 6 days at 5° C., beforedrying.

4) 176.8 g of the wet gel from 3) was cut into smaller pieces andtransferred under methanol to a ½ L pressure vessel (½ L flow reactor,equipped with heating jacket and metal frits in both ends, from Thardesigns). There was flowed with ½ L of methanol at 0.5 mL/min. Then thetemperature in the heating jacket was raised to 50° C. and the pressureraised to 100 bars, at a rate of 3 bars/min. During 8 hours at 50° C.and 100 bars, 2½ kg of CO₂ was flowed through the vessel at a rate of5-7 mL/min measured at 10° C. After flowing the pressure was slowlyreleased during several hours. The weight of the supercritical driedaerogel was 18.685 g.

Example 3 Antifreeze Protein Incorporated in a Silica Aerogel ForWater-Borne Coatings

Production of antifreeze proteins have recently been described in apatent application disclosed by its owner RUC. The antifreeze proteinfrom Rhagium mordax may be taken as an example. The protein has beenexpressed in a microorganism. The antifreeze protein is thereforeavailable in a solution similar to the Espherase used in example 1 and2. The procedure for creation of aerogels incorporating antifreezeproteins will therefore substantially be the same as used for Espherase.

Example 4 Bacteriophages Incorporated in a Silica Gel

A suspension of Escherichia coli T2 bacteriophages 10¹² pr ml can beused as replacement for the Espherase solutions in the proceduresdescribed in example 1 and 2. The low temperature and pressure used inthe formation of the aerogel is of critical importance for the viabilityof the bacteriophages during the aerogel formation.

Example 5 Enzymes Incorporated in a Silica Aerogel For Solvent BasedPaints

1) 57.4 g TMOS (Tetramethyl orthosilicate 98% from Aldrich) and 229.2 gMethanol (Methanol reagent PH. EUR. from Bie & Berntsen) was mixed on amagnetic stirrer in a 1 L erlenmeyer flask for 15 minutes.

2) 200 mL Esperase solution (HPF from Novozymes) was dialysed and freezedried. There was obtained 18.40 g dry enzyme, which was dissolvedquickly (about 5 minutes) in 60 mL milli-Q water and the viscoussolution was added drop wise to 1) during mixing. The solution was mixedfor 15 minutes additionally.

3) 0.933 g of ammonium hydroxide (28-30% solution from Bie & Berntsen)dissolved in 7.50 g of milli-Q water was added dropwise to 2) duringmixing at full speed (1500 RPM) on the magnetic stirrer. Afteradditionally 2 minutes of mixing, the white opaque solution wastransferred into a 1 L bluecap bottle. After a ½ hour, the gelation tookplace and the obtained 410 mL gel was aged in methanol, for 24 hours atroom temperature, before drying.

4) 287 g of the wet gel from 3) was cut into smaller pieces andtransferred under methanol to a ½ L pressure vessel (½ L flow reactor,equipped with heating jacket and metal frits in both ends, from Thardesigns). There was flowed with ½ L of methanol at 0.5 mL/min. Then thetemperature in the heating jacket was raised to 50° C. and the pressureraised to 100 bars, at a rate of 3 bars/min. During 8 hours at 50° C.and 100 bars, 2½ kg of CO₂ was flowed trough the vessel at a rate ofapproximately 6 mL/min measured at 10° C. After flowing the pressure wasslowly released during several hours. The weight of the supercriticaldried aerogel was 34.23 g.

Example 6 Enzymes Incorporated in a Silica Aerogel For Water BasedPaints

1) 28.6 g TMOS (Tetramethyl orthosilicate 98% from Aldrich) and 111.0 gMethanol (Methanol reagent PH. EUR. from Bie & Berntsen) was mixed on amagnetic stirrer in a 1 L erlenmeyer flask for 15 minutes.

2) 0.752 g PVA (Polyvinyl alcohol, with a degree of polymerisation of2000 and a degree of hydrolysation of 86-89 mol %, from Fluka Chemika)was wetted with 5 mL methanol and dissolved I 30 mL milli-Q water. 100mL Esperase solution (HPF from Novozymes) was dialysed and freeze dried.There was obtained 6.279 g dry enzyme, which was dissolved quickly(about 5 minutes) in the PVA solution and the obtained viscous enzymesolution was added drop wise to 1) during mixing. The solution was mixedfor 15 minutes additionally.

3) 0.517 g of ammonium hydroxide (28-30% solution from Bie & Berntsen)dissolved in 3.737 g of milli-Q water was added dropwise to 2) duringmixing at full speed (1500 RPM) on the magnetic stirrer. Afteradditionally 2 minutes of mixing, the white opaque solution wastransferred into a 1 L bluecap bottle. After 15 minutes the gelationtook place and the obtained 200 mL gel was aged in methanol, for 24hours at room temperature and additionally 6 days at 5° C., beforedrying.

4) 176.8 g of the wet gel from 3) was cut into smaller pieces andtransferred under methanol to a ½ L pressure vessel (½ L flow reactor,equipped with heating jacket and metal frits in both ends, from Thardesigns). There was flowed with ½ L of methanol at 0.5 mL/min. Then thetemperature in the heating jacket was raised to 50° C. and the pressureraised to 100 bars, at a rate of 3 bars/min. During 8 hours at 50° C.and 100 bars, 2½ kg of CO₂ was flowed trough the vessel at a rate of 5-7mL/min measured at 10° C. After flowing the pressure was slowly releasedduring several hours. The weight of the supercritical dried aerogel was18.685 g.

Example 7 Enzymes Incorporated in a Silica Gel Structure For Water BasedPaints

1) 3.82 g TMOS (Tetramethyl orthosilicate 98% from Aldrich) and 20,03 gProperase solution (Properase 1600 L from Danisco) was mixed on amagnetic stirrer in a 100 mL erlenmeyer flask for 15 minutes.

2) 0.1368 g of ammonium hydroxide (28-30% solution from Bie & Berntsen)dissolved in a mixture of 1.02 g of milli-Q water and 4.01 g of PG(Propylene glycol 98% from Fluka), was added dropwise to 1) duringmixing at full speed (1500 RPM) on the magnetic stirrer. A transparentorange-brown gel was formed after additionally 50 seconds of mixing.

After aging for 24 hours the gel seems more opaque. The gel was storedin refrigerator at 5° C. until it was used for preparation of awater-based paint. No syneresis was observed.

Example 8 Enzymes Incorporated in a Polymer Reinforced Silica AerogelFor Water-Based Paints

1) 4.68 g TEOS (Tetraethyl orthosilicate 98% from Fluka), 1.00 g ofmilli-Q water and 1.00 g of a 0.1 M hydrochloric acid solution was mixedon a magnetic stirrer in a 100 mL erlenmeyer flask for 15 minutes.

2) 1.46 g of a 5% (w/w) solution of PVA (Polyvinyl alcohol, with adegree of polymerisation of 2000 and a degree of hydrolysation of 86-89mol %, from Fluka Chemika) was mixed with 3,98 g PG (Propylene glycol98% from Fluka) and 13.66 mg ammonium hydroxide (28-30% solution fromBie & Berntsen). The mixture was added dropwise to 2) duringcontinuously stirring. After additionally 2 minutes of mixing pH wasmeasured with indicator paper (from Toyo Roshi Co, Ltd) to be between5.0 and 5.5.

3) 12.5 mL properase solution (Properase 1600 L from Danisco) was addedslowly during mixing and mixing was allowed to proceed for additionally15 minutes.

4) 12 mL ammonium hydroxide (28-30% solution from Bie & Berntsen) wasdissolved in 2 mL of milli-Q water and added dropwise to 3) duringmixing at full speed (1500 RPM) on the magnetic stirrer. Afteradditionally 2 minutes of mixing at full speed, the obtained transparentorange-brown sol was transferred into a 100 mL bluecap bottle.

After 7 minutes the gelation took place and the obtained 25 mLorange-brown gel was still transparent after 24 hours aging at roomtemperature. The gel was stored in refrigerator at 5° C. until it wasused for preparation of a water-based paint. Only very little syneresisseems to take place during aging and storing.

Example 9 Aerogels Including Enzymes, Bacteriophages and/or Other ActiveComponents in a Water-Borne Coating

1) Water-Borne Antifouling Composition

In water borne paints the inorganic aerogels have until now been oflittle use. It has been observed that in polishing water-borne paintsthe aerogel increases the water uptake, reduce hardness and thus mayincrease the rate of polishing to a level unacceptable for commercialvessels and fast sailing pleasure boats.

In this case an aerogel with a polymer included was introduced into awater-borne yacht paint composition.

Component Amount in weight-%  1. Propylenglycol (co-solvent) 10  2.Water 10  3. Orotan 850 EL, 30% (dispersion agent) 1.4  4. TEA (amine)0.2  5. Aerogel AP50 1  6. Zinkoxide Code 620 (pigment) 43  7.Micro-talc A.T. 1 (filler) 5  8. Lipaton X 6030* (acrylic emulsion) 5 9. Synaqua 2070, 53% (alkyd emulsion) 15 10. Tributoxyethylphosphate(coalescing agent) 0.25 11. Mn-Hydro-cure 9% (direr) 0.38 12. Co-HEX-CEM10% (drier) 0.14 13. Tego 1488 (anti-foaming agent) 0.2 14. Water 5.315. Aerysol RM 825 (thickener) 3 13. In-can preservation 0.14 Totally100

When comparing the properties of the above composition with acomposition without polymer in the aerogel the following results areachieved:

-   -   Water uptake (in artificial sea water) is not increased when        increasing the aerogel (with polymer) content from 0,5 weight-%        to 1 weight-%    -   Water uptake(in artificial sea water) is increased when        increasing the aerogel (without polymer) content from 0,5        weight-% to 1 weight-%    -   The aerogel in itself increases degradation and thus polishing        rate when introduced in the composition    -   An aerogel including a polymer reduces the polishing effect to        some extent.

This composition contains two binders, where one is degrading (alkyde)and the other is giving hardness (acrylic). The alkyde dispersion can ofcourse be omitted if another binder is included that can contribute todegradation in sea water and thus to the polishing rate. The number ofbinders can be extended to three or more. The binders can be dispersionscontaining, alkyde or other polyesters, acrylic/acrylic copolymers,polyvinylacetate, urethanes, rosins, water-soluble resins etc.

Furthermore, the pigment chosen in this case contributes to thepolishing rate. Other choices of pigments could contain other metals astitanium (rutile and/or anatase), iron, manganese, molybdenum, etc. Itis also possible to use organic pigments in the composition. Likewisecan other fillers, film formers (coalescing agents), co-solvents,thickeners and other additives be used.

The aerogel should be regarded as an additive, where the amount normallywill be under 5% and in most cases significantly less than 2%. Thereason is that the aerogel introduces a different rheological behaviourof the wet product as well as other mechanical properties of the drycoating.

It should be noted that the dispersion agent is chosen to fit to thepigment in the specific type of paint/coating. In this connection theaerogel can have an impact on the choice and amount of dispersion agentdue to a large surface area.

The amount of each component is optimised in the specificcomposition/formulation.

To make a formulation that have the functionality wanted is thus notonly a question of using one or the other binder, pigment etc., but aquestion of choosing an aerogel which fits for the purpose and dosingthe amount of formulated aerogel in the correct amount to achieve thephysical parameters and the protection against biological growth neededfor the application in question.

The same coating can be produced with a wet gel, see table 1b. Choosinga wet gel has several advantages.

-   -   The raw material itself becomes cheaper as a production step in        the gel production process is omitted.    -   Dust from the aerogel is avoided in the coating production        process.    -   The wet gel can be designed for different paint systems using        different solvent/liquid mixtures.

TABLE 1B Component Amount in weight-%  1. Propylenglycol (co-solvent) 5 2. Water 20  3. Orotan 850 EL, 30% (dispersion agent) 1.4  4. TEA(amine) 0.2  5. Aerogel wet, (including an active compund) 10  6.Zinkoxide Code 620 (pigment) 43  7. Micro-talc A.T. 1 (filler) 5  8.Lipaton X 6030* (acrylic emulsion) 5  9. Synaqua 2070, 53% (alkydemulsion) 15 10. Tributoxyethylphosphate (coalescing agent) 0.25 11.Mn-Hydro-cure 9% (direr) 0.25 12. Co-HEX-CEM 10% (drier) 0.09 13. Tego1488 (anti-foaming agent) 0.2 14. Water 0.3 15. Acrysol RM 825(thickener) 3 13. In-can preservation 0.14 Totally 100

In this example with a water-borne antifouling composition importantphysical parameters for the coating film are:

-   -   Polishing rate; is decided by the type of vessel or pleasure        boat the product is aimed for. Thus a low polishing rate for        ships sailing continuously and a higher polishing rate for the        yacht market.    -   Water uptake; a water-borne coating should not exceed 20        weight-% of water pick-up when exposed to artificial sea water.        A high amount of water in the film reduces hardness and        increases the degradation where these effects will reduce the        protective period and thus be fatal for the coating. As an        example a yacht paint should function for at least one sailing        season.    -   Hardness; the pendulum hardness should be of the same level as        other commercial products used in the application area aimed        for.

This type of composition could also be formulated as a matte clearcoating to be used either as an anti-fouling coating or as a coating ator above the water line.

2) Water-Borne Architectural Paint For Walls and Ceilings

One starting formulation is:

Component Amount in weight-%  1. Propylenglycol (co-solvent) 10  2.Water 10  3. Orotan 850 EL, 30% (dispersion agent) 1.4  4. TEA (amine)0.2  5. Aerogel AP50 1  6. Zinkoxide Code 620 (pigment) 43  7.Micro-talc A.T. 1 (filler) 5  8. Lipaton X 6030* (acrylic emulsion) 5 9. Synaqua 2070, 53% (alkyd emulsion) 15 10. Tributoxyethylphosphate(coalescing agent) 0.25 11. Mn-Hydro-cure 9% (direr) 0.38 12. Co-HEX-CEM10% (drier) 0.14 13. Tego 1488 (anti-foaming agent) 0.2 14. Water 5.315. Acrysol RM 825 (thickener) 3 13. In-can preservation 0.14 Totally100

The binder emulsion and binder emulsion amount is chosen in accordancewith the use of the paint. In the same way is the type and amount ofpigment and fillers chosen.

Examples of binder emulsions that might be used are styrene-acrylics,acrylic-copolymers, vinyl acetates, vinyl acetate/ethylene, alkyds,PU-alkyds, polyurethanes etc. Also in this case water-soluble polymerscan be included in a formulation. Due to environmental regulations it isexpected that cosolvents and coalescing agents will be minimizedfurther.

The largest use is expected were anti-bacterial surfaces are needed.This means that making a wall paint for hospitals might include anaerogel with bacteriophages (and/or enzymes) that can reduce the risk inconnection with certain deceases. In the same way may designed aerogelswith active compounds be used in wet rooms.

3) Water-Borne Wood Stain and Wood Finishes

One starting formulation is:

Approximate amount in Component weight-% Binder Primal AC-337 (acrylicemulsion) 42.0 Dispersion agent Tego 740 W 0.4 Defoamer Foamex 1488 0.2Water 35.76 Propylene glycol 5.0 Filler Microdol 1 10.0 Texanol 1.0Amine 0.2 Thickener RM 825 0.5 Aerogel, with 5% PEG or PVA and/or 0.8active compound(s) Hostatint oxide red E-OR 4.0 In-can preservation 0.14Totally 100.0

A wood stain is basically prepared in the same manner as anarchitectural paint for walls and ceilings. Very often is an alkydemulsion used often in combination with an acrylic emulsion. It can alsobe a hybride binder emulsion, e.g. core-shell technology. Furthermore,the possibility of using water-soluble alkyd resins is available. Alkydpolyurethane emulsions, polyurethane dispersions alone or in combinationwith acrylic emulsions/water-dilutable polyester resins orself-crosslinking acrylic emulsion among other possibilities can also bementioned. 2C systems are an option. In this type of composition nanoparticles may also be present to achieve specific physical properties.Again a designed aerogel will be necessary to achieve the wanted (slow)degradation over time matching the protection against biofilm andbiological growth for the given application. Even though most of theapplications on wood is expected to be outdoors there will be specificapplications indoors as well (i.e. floors, windows).

4) Water-Borne Roof Composition

The difference in the composition from a wood stain is mainly the choiceof binder and pigmentation. But the problem is the same with regard tobiological growth. Which means that a designed aerogel with enzyme(s)and/or other active compounds may be used in this type of coating with aslow degradation rate. We would expect that the same type aerogel as forwood stain should be used.

One starting formulation is:

Component Approximate amount in weight-% PVA binder Acronal S 300, 50%48.0 Water 14.86 Dispersing agent Tego 740 W 0.4 Defoamer Tego foamex1488 0.4 Titanium dioxide Kemira RDI-S 5.6 Filler Talc AT 1 1.3 FillerMicrodol 1 25.0 Texanol 1.0 Thickening agent RM 825 0.5 Aerogel (with 5%PEG/PVA and 0.8 active compound(s)) Hostatint Black E-BLN 2.0 In-canpreservation 0.14 Totally 100.0

5) Water-Borne Coatings For Materials That Are Intended For Contact WithFood

In this case, will the components in the water-borne coating have to beapproved of, according to EU regulation at the time being. Asbacteroiophages can be used against the Listeria monocytogenes bacteriait may also be used against Salmonella, which may be of interest inconnection with materials in direct as well as in-direct contact withfood.

The use could include prints on materials as paper, plastic, metal foilsetc.

Furthermore, the use is not restricted to one specific printing methodor one specific use of printed matter.

6) Other Water-Borne Products

It is expected that the use of aerogels can be extended to floorpolishes, glues, lacquers, primers, sealers, anti-graffiti products etc.

It is also expected that aerogels including active compounds can be ofinterest for coatings used on plastic, concrete and steel. Theapplications can be both for DIY (do-it-yourself) products as well asfor industrial applications.

7) Extending the Practical Use of Water-Borne Coatings

Using aerogels including antifreeze protein might extend the use ofwater-borne products with regard to application. Being able to apply aproduct at low temperatures and still get film forming is of greatinterest as well as being able to extend shelf life at low temperatures.

Example 10 Aerogels Including Enzymes, Bacteriophages and/or OtherActive Compounds in a Solvent-Based Coating

1) Solvent-Based Wood Stain and Wood Finishes

One starting formulation is:

Component Approximate amount in weight-% White spirit 15.0 Dispersionagent Tego 710 0.4 Filler Microdol 1 46.0 Binder Alkydal F 681 31.8Thickener Luvogel SA1 1.0 Aerogel (with active compound(s)) 0.8 DrierCoZirk 69 2.0 Pigment paste Hostatint Oxide red 3.0 Totally 100.0

A solvent-based wood stain is typically made with an alkyd bindersystem. It can also be combined with other binders (eg. Polyesters,modified alkyds, rosins and vegetable oils). Binder hybrids and/orcopolymers are also a possibility.

In this case will a designed aerogel with enzyme(s) and/or other activecompounds be used in a coating with a slow degradation rate. In thecomposition especially choice of binders is clearly dependent of theapplication in question. Industrial coatings differ significantly fromdo-it-yourself products. High solids products are of course important infuture.

Floor compositions are often solvent-based 2C binder systems.

2) Industrial Compositions

Thermoplastic acrylic binders can be used in industrial compositions.Alkyds have in this type of application a short to medium oil length,mainly due to the drying time. Again the binders are oftenfunctionalised and can be used with different chemistry and in differentcombinations. Industrial compositions include products for coil coatingand heavy-duty applications.

The use of aerogels in industrial applications is obvious with regard tothe rheological properties achieved. Still the choice of activecompounds has to be in accordance with the use of the coating.

Example 11 Aerogels Including Enzymes, Bacteriophages and/or OtherActive Components in Other Coatings

Aerogels may find use in coatings that are dried in another manner thansolvent-based or water-borne coatings. Examples are UV (or EB) dryingcoatings for floors and furniture. Here degradation might not be thepurpose, but basically to achieve an antibacterial effect. The dryingprocess can also be a combination of physical drying and radiation.

1. A composition comprising a gel wherein is entrapped at least oneactive component such that release of said at least one active componentfrom said composition is substantially caused by degradation of saidgel.
 2. The composition according to claim 1, wherein said gel is asolvent containing gel an aerogel, a xerogel or a cryogel.
 3. Thecomposition according to claim 1 wherein said at least one activecomponent substantially is not liberated from said composition bydiffusion out of said composition.
 4. The composition according to claim1, wherein said degradation of the gel is caused by mechanical wear, byhydrolysis, by UV radiation or by ultrasonication of the composition. 5.The composition according to claim 1, comprising two or moreinterpenetrating networks or semi interpenetrating networks of gelforming materials.
 6. The composition according to claim 5, wherein saidgel forming materials are selected from metal alcoxides based on Sc, Ti,V, Cr, Mn, Fe, Co, Y, Zr, Nb, Ru, Hf, Ta, W, Re, Si, Al, Ge, In, La, Pr,Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and/or organic polymers suchas polyvinyl alcohol, polyethylene glycol, polylactic acid,polypropylene glycol, polyvinylpyrilidone and from organic crosslinkers.7. The composition according to claim 1, comprising at least one enzymeor protein.
 8. The composition according to claim 7 wherein said atleast enzyme is selected from the group consisting ofhemicellulolytically active enzymes, amylolytically active enzymesand/or cellulolytically active enzymes.
 9. The composition according toclaim 1, comprising at least one bacteriophage.
 10. The compositionaccording to claim 9 comprising at least two different bacteriophages.11. (canceled)
 12. (canceled)
 13. Film comprising the compositionaccording to claim
 1. 14. The film according to claim 13, which is aliquid film or a solidified liquid film.
 15. (canceled)
 16. A solventcontaining gel functioning as an antifouling, antibacterial orbiofouling/bioprotective agent where the solvent composition in the Solstate has been selected to be compatible with the paint or coating to beprepared.